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Bopegamagea S, Kacerov M, Tamborc V, Musilovab I,
Sarmirovaa S, Snelerse !, et al" Preterm prelabor
rupture of membranes (PPROM) is not associate#it$
presence of viral genomes in t$e amniotic %ui"
&ournal of 'linical Virolog(" )*+,"
Background- T$e role of viral infections in preterm
prelabor rupture of t$e membranes (PPROM) is
notestablis$e" Stuies on t$e presence of viral
genomes in t$e amniotic %ui (./) collecte in
pregnanciescomplicate b( PPROM s$o#
contraictor( outcomes"
Objectives- To investigate ./ samples of PPROM
pregnancies for t$e presence of viral genomes"
Study design- ./ samples from patients #it$ PPROM
#ere collecte uring a 01(ear ()**23)*+)) obser1
vational stu(" +40 #omen #ere inclue #it$
selection criteria of singleton pregnanc(, PPROM,
anmaternal age of +2 (ears an above" P'R #as
use for etection of $uman c(tomegalovirus
(5'MV),$erpes simple6 virus (5SV), parvovirus B+7,
$uman aenoviruses (5.V), enteroviruses (!V) an
$umanparec$ovirus (5PeV)" T$e selection of t$ese
viral targets #as base on literature regaring
screening of./ for presence of viral genomes"
Results- Onl( a single sample #as positive out of t$e
+40 teste ./s, 5'MV 89. #as etecte"
Conclusions- PPROM is not associate #it$ active
viral infections"
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Background- T$e role of viral infections in preterm
prelabor rupture of t$e membranes (PPROM) is
notestablis$e" Stuies on t$e presence of viral
genomes in t$e amniotic %ui (./) collecte in
pregnanciescomplicate b( PPROM s$o#
contraictor( outcomes"
Objectives- To investigate ./ samples of PPROM
pregnancies for t$e presence of viral genomes"
Study design- ./ samples from patients #it$ PPROM
#ere collecte uring a 01(ear ()**23)*+)) obser1
vational stu(" +40 #omen #ere inclue #it$
selection criteria of singleton pregnanc(, PPROM,
anmaternal age of +2 (ears an above" P'R #as
use for etection of $uman c(tomegalovirus
(5'MV),$erpes simple6 virus (5SV), parvovirus B+7,
$uman aenoviruses (5.V), enteroviruses (!V) an
$umanparec$ovirus (5PeV)" T$e selection of t$ese
viral targets #as base on literature regaring
screening of./ for presence of viral genomes"
Results- Onl( a single sample #as positive out of t$e
+40 teste ./s, 5'MV 89. #as etecte"
Conclusions- PPROM is not associate #it$ active
viral infections"
/u:imoto T, Parr( S, ;rbane< M, Sammel M, Macones
=, Kuivaniemi 5, et al" . Single 9ucleotie
Pol(morp$ism in t$e Matri6 Metalloproteinase1+ (MMP1
+) Promoter In%uences .mnion 'ell MMP1+ !6pression
an Ris< for Preterm Premature Rupture of t$e /etal
Membranes" T5! &O;R9.> O/ BIO>O=I'.>
'5!MISTR?" )**)@)44"
Interstitial collagen gives fetal membranes tensile
strengt$, an membrane rupture $as been attribute
to collagen egraation" . pol(morp$ism at +A*4 in
t$e matri6 metalloproteinase1+ (MMP1+) promoter (an
insertion of a guanine (=)) creates a core !ts bining
site an increases promoter activit(" Be investigate
#$et$er t$is pol(morp$ism is functionall( signiCcant
for MMP1+ e6pression in amnion cells an #$et$er it is
associate #it$ preterm premature rupture of t$e
membranes (PPROM)" T$e )= promoter $a D)1fol
greater activit( t$an t$e += allele in amnion
mesenc$(mal cells an BIS5 amnion cells" P$orbol
+)1m(ristate +,1acetate (PM.) increase
mesenc$(mal cell nuclear protein bining #it$
greater aEnit( to t$e )= allele" Inuction of MMP1+
mR9. b( PM. #as signiCcantl( greater in cells #it$ a
+=F)= or )=F)= genot(pe compare #it$ cells
$omoG(gous for t$e += allele" B$en treate #it$ PM.,
t$e +=F)= an )=F)= cells prouce greater amounts
of MMP1+ protein t$an +=F+= cells"
. signiCcant association #as foun bet#een fetal
carriage of a )= allele an PPROM"
Be conclue t$at t$e )= allele $as stronger promoter
activit( in amnion cells, t$at it confers increase
responsiveness of amnion cells to stimuli t$at inuce
MMP1+, an t$at t$is pol(morp$ism contributes to t$e
ris< of PPROM"
Interstitial collagen gives fetal membranes tensile
strengt$, an membrane rupture $as been attribute
to collagen egraation" . pol(morp$ism at +A*4 in
t$e matri6 metalloproteinase1+ (MMP1+) promoter (an
insertion of a guanine (=)) creates a core !ts bining
site an increases promoter activit(" Be investigate
#$et$er t$is pol(morp$ism is functionall( signiCcant
for MMP1+ e6pression in amnion cells an #$et$er it is
associate #it$ preterm premature rupture of t$e
membranes (PPROM)" T$e )= promoter $a D)1fol
greater activit( t$an t$e += allele in amnion
mesenc$(mal cells an BIS5 amnion cells" P$orbol
+)1m(ristate +,1acetate (PM.) increase
mesenc$(mal cell nuclear protein bining #it$
greater aEnit( to t$e )= allele" Inuction of MMP1+
mR9. b( PM. #as signiCcantl( greater in cells #it$ a
+=F)= or )=F)= genot(pe compare #it$ cells
$omoG(gous for t$e += allele" B$en treate #it$ PM.,
t$e +=F)= an )=F)= cells prouce greater amounts
of MMP1+ protein t$an +=F+= cells"
. signiCcant association #as foun bet#een fetal
carriage of a )= allele an PPROM"
Be conclue t$at t$e )= allele $as stronger promoter
activit( in amnion cells, t$at it confers increase
responsiveness of amnion cells to stimuli t$at inuce
MMP1+, an t$at t$is pol(morp$ism contributes to t$e
ris< of PPROM"
=eta$un 8, Stric<lan 8, .nant$ 'V, /assett M&,
Sac<s 8., Kirb( RS, et al" Recurrence of preterm
premature rupture of membranes in relation to
interval bet#een pregnancies" )*+*
OBJECTIVE- T$e purpose of t$is stu( #as to
e6amine #$et$er t$e recurrence ris< of preterm
premature rupture of membranes (PPROM) is
moiCe b( t$e interpregnanc( interval (IPI)"
ST!" !ESI#$- Be use t$e Missouri +7273+774
longituinall( lin<e ata to e6amine t$e
recurrence ris< of PPROM in #omen #it$ Crst ) (n
+H*,7)7) an Crst , (n ,*,*++) successive
pregnancies" Race1speciCc recurrence ris<s #ere
e6amine" .:uste os ratios (OR) #ere use to
estimate ris<s"
RES%TS- Ris<s of PPROM in t$e secon
pregnanc( among #omen #it$ an #it$out
previous PPROM #ere H"4I an )",I,
respectivel(, among #$ite #omen (OR, 2"4@ 7HI
conCence interval, A"43++"0) an +*",I an
0",I, respectivel(, among .frican .merican
#omen (OR, 4")@ 7HI conCence interval, H"+3
+*"+)" S$ort IPI #as associate #it$ increase ris<
for PPROM recurrence, #it$ substantiall( $ig$er
ris< for .frican .merican #omen t$an #$ite
#omen" 5o#ever, long IPI #as associate #it$
increase recurrence among .frican .merican
#omen"
CO$C%SIO$- Bomen #it$ previous PPROM are
at increase ris< for recurrence, an a s$ort IPI is
associate #it$ increase ris<"
OBJECTIVE- T$e purpose of t$is stu( #as to
e6amine #$et$er t$e recurrence ris< of preterm
premature rupture of membranes (PPROM) is
moiCe b( t$e interpregnanc( interval (IPI)"
ST!" !ESI#$- Be use t$e Missouri +7273+774
longituinall( lin<e ata to e6amine t$e
recurrence ris< of PPROM in #omen #it$ Crst ) (n
+H*,7)7) an Crst , (n ,*,*++) successive
pregnancies" Race1speciCc recurrence ris<s #ere
e6amine" .:uste os ratios (OR) #ere use to
estimate ris<s"
RES%TS- Ris<s of PPROM in t$e secon
pregnanc( among #omen #it$ an #it$out
previous PPROM #ere H"4I an )",I,
respectivel(, among #$ite #omen (OR, 2"4@ 7HI
conCence interval, A"43++"0) an +*",I an
0",I, respectivel(, among .frican .merican
#omen (OR, 4")@ 7HI conCence interval, H"+3
+*"+)" S$ort IPI #as associate #it$ increase ris<
for PPROM recurrence, #it$ substantiall( $ig$er
ris< for .frican .merican #omen t$an #$ite
#omen" 5o#ever, long IPI #as associate #it$
increase recurrence among .frican .merican
#omen"
CO$C%SIO$- Bomen #it$ previous PPROM are
at increase ris< for recurrence, an a s$ort IPI is
associate #it$ increase ris<"
Table Of Refrence
5am 8Pv, 5e(en &>v, Opmeer B', Muler .>M,
Moonen RM&, Bee< &v, et al" Management of late1
preterm premature rupture of membranes- t$e
PPROM!JI>1) trial" )*+)"
OBJECTIVE- T$e evience for t$e management of
near term prelabor rupture of membranes is poor"
/rom &anuar( )**4 until September )**7, #e
performe t$e PPROM !6pectant Management
versus Inuction of >abor (PPROM!JI>) trial" In t$is
trial, #e s$o#e t$at in #omen #it$ preterm
prelabor rupture of membranes (PPROM), t$e
incience of neonatal sepsis #as lo#, an t$e
inuction of labor (Io>) i not reuce t$is ris<"
Because t$e PPROM!JI> trial #as unerpo#ere an
because of a lo#er1t$an1e6pecte incience of
neonatal sepsis, #e performe a secon trial
(PPROM!JI>1)), aiming to ranomiGe )** patients to
improve t$e evience in near1term PPROM"
ST!" !ESI#$- In a nation#ie multicenter stu(,
nonlaboring #omen #it$ PPROM bet#een ,0 an ,4
#ee<sK gestational age #ere eligible for inclusion"
Patients #ere ranomiGe to Io> or e6pectant
management (!M)" T$e primar( outcome measure
#as neonatal sepsis" R!S;>TS- /rom 8ecember )**7
until &anuar( )*++, #e ranomiGe
+** #omen to Io> an 7H to !M" 9eonatal sepsis #as
seen in , neonates (,"*I) in t$e Io>1group versus 0
neonates (0"+I) in t$e !M group (relative ris<, *"40@
7HI conCence interval, *"+43,"))" One of t$e
sepsis cases in t$e Io> group resulte in neonatal
eat$ because of asp$(6ia" T$ere #ere no
signiCcant iLerences in seconar( outcomes"
CO$C%SIO$- T$e ris< of neonatal sepsis after
PPROM near term is lo#" Inuction of labor oes not
reuce t$is ris<"
OBJECTIVE- T$e evience for t$e management of
near term prelabor rupture of membranes is poor"
/rom &anuar( )**4 until September )**7, #e
performe t$e PPROM !6pectant Management
versus Inuction of >abor (PPROM!JI>) trial" In t$is
trial, #e s$o#e t$at in #omen #it$ preterm
prelabor rupture of membranes (PPROM), t$e
incience of neonatal sepsis #as lo#, an t$e
inuction of labor (Io>) i not reuce t$is ris<"
Because t$e PPROM!JI> trial #as unerpo#ere an
because of a lo#er1t$an1e6pecte incience of
neonatal sepsis, #e performe a secon trial
(PPROM!JI>1)), aiming to ranomiGe )** patients to
improve t$e evience in near1term PPROM"
ST!" !ESI#$- In a nation#ie multicenter stu(,
nonlaboring #omen #it$ PPROM bet#een ,0 an ,4
#ee<sK gestational age #ere eligible for inclusion"
Patients #ere ranomiGe to Io> or e6pectant
management (!M)" T$e primar( outcome measure
#as neonatal sepsis" R!S;>TS- /rom 8ecember )**7
until &anuar( )*++, #e ranomiGe
+** #omen to Io> an 7H to !M" 9eonatal sepsis #as
seen in , neonates (,"*I) in t$e Io>1group versus 0
neonates (0"+I) in t$e !M group (relative ris<, *"40@
7HI conCence interval, *"+43,"))" One of t$e
sepsis cases in t$e Io> group resulte in neonatal
eat$ because of asp$(6ia" T$ere #ere no
signiCcant iLerences in seconar( outcomes"
CO$C%SIO$- T$e ris< of neonatal sepsis after
PPROM near term is lo#" Inuction of labor oes not
reuce t$is ris<"
Mercer BM, 'rouse 8T, =olenberg R>, Mioovni< M, Mapp
8', Meis P&, et al" T$e antibiotic treatment of PPROM stu(-
s(stemic maternal an fetal mar<ers an perinatal
outcomes" )*+)"
OBJECTIVE- Be soug$t to correlate maternal an cor bloo
c(to<ine an intercellular a$esion molecule1+ levels #it$
antibiotic e6posure an perinatal outcomes after
conservativel( manage preterm premature rupture of t$e
membranes"
ST!" !ESI#$- 'onservativel( manage #omen #it$
preterm premature rupture of t$e membranes at )01,)
#ee<s $a bloo sampling at ranomiGation (n )))) an
eliver( (n +)+)" Plasma from t$ese, an umbilical cor
bloo (n +7A), #as store at 34*M'" Interleu<in (I>)1A, I>1+*,
granuloc(te colon(1stimulating factor (=1'S/), tumor
necrosis factor1 , an intercellular a$esion molecule1+ levels
#ere assesse for associations #it$ antibiotic treatment,
latenc(, amnionitis, neonatal sepsis, pneumonia, an
composite neonatal morbiit("
RES%TS- 'or bloo I>1A an =1'S/ #ere $ig$er t$an
maternal levels" .ntibiotic treatment lo#ere onl( maternal
=1'S/ (P "*+)" !levate maternal c(to<ine levels #ere
associate #it$ eliver( #it$in 4 a(s an #it$ evelopment
of c$orioamnionitis" .ll umbilical cor bloo mar<ers #ere
increase #it$ amnionitis (P "*+ for eac$)" 9o maternal
mar<er #as associate #it$ neonatal morbiities" 'or =1
'S/ an I>1A #ere increase #it$ neonatal sepsis #it$in 4)
$ours of birt$ (P "**0 for bot$), an #it$ composite
neonatal morbiit( (P "**+ an "**), respectivel()" Maternal
an umbilical cor c(to<ine levels emonstrate lo#
preictive values for perinatal outcomes"
CO$C%SIO$- ;mbilical cor bloo c(to<ine values are
$ig$er t$an maternal levels, suggesting signiCcant
fetalFplacental contribution" Maternal an umbilical cor
c(to<ine levels are not aeNuatel( preictive to be use
clinicall("
OBJECTIVE- Be soug$t to correlate maternal an cor bloo
c(to<ine an intercellular a$esion molecule1+ levels #it$
antibiotic e6posure an perinatal outcomes after
conservativel( manage preterm premature rupture of t$e
membranes"
ST!" !ESI#$- 'onservativel( manage #omen #it$
preterm premature rupture of t$e membranes at )01,)
#ee<s $a bloo sampling at ranomiGation (n )))) an
eliver( (n +)+)" Plasma from t$ese, an umbilical cor
bloo (n +7A), #as store at 34*M'" Interleu<in (I>)1A, I>1+*,
granuloc(te colon(1stimulating factor (=1'S/), tumor
necrosis factor1 , an intercellular a$esion molecule1+ levels
#ere assesse for associations #it$ antibiotic treatment,
latenc(, amnionitis, neonatal sepsis, pneumonia, an
composite neonatal morbiit("
RES%TS- 'or bloo I>1A an =1'S/ #ere $ig$er t$an
maternal levels" .ntibiotic treatment lo#ere onl( maternal
=1'S/ (P "*+)" !levate maternal c(to<ine levels #ere
associate #it$ eliver( #it$in 4 a(s an #it$ evelopment
of c$orioamnionitis" .ll umbilical cor bloo mar<ers #ere
increase #it$ amnionitis (P "*+ for eac$)" 9o maternal
mar<er #as associate #it$ neonatal morbiities" 'or =1
'S/ an I>1A #ere increase #it$ neonatal sepsis #it$in 4)
$ours of birt$ (P "**0 for bot$), an #it$ composite
neonatal morbiit( (P "**+ an "**), respectivel()" Maternal
an umbilical cor c(to<ine levels emonstrate lo#
preictive values for perinatal outcomes"
CO$C%SIO$- ;mbilical cor bloo c(to<ine values are
$ig$er t$an maternal levels, suggesting signiCcant
fetalFplacental contribution" Maternal an umbilical cor
c(to<ine levels are not aeNuatel( preictive to be use
clinicall("
Morris &M, Roberts '>, 'ro#t$er '., Buc$anan S>, 5enerson 8&, Sal<el ="
Protocol for t$e immeiate eliver( versus e6pectant care of #omen #it$
preterm prelabour rupture of t$e membranes close to term (PPROMT)"
)**H
Background- Preterm prelabour rupture of membranes (PPROM)
complicates up to )I of all pregnancies an is t$e cause of 0*I of all
preterm birt$s" T$e optimal management of #omen #it$ PPROM prior to
,4 #ee<s, is not <no#n" /urt$ermore, iversit( in current clinical practice
suggests uncertaint( about t$e appropriate clinical management" T$ere
are t#o options for managing PPROM, e6pectant management (a #ait an
see approac$) or earl( planne birt$" Infection is t$e main ris< for #omen
in #$ic$ management is e6pectant" T$is ris< nee to be balance against
t$e ris< of iatrogenic prematurit( if earl( eliver( is planne" T$e iLerent
treatment options ma( also $ave iLerent $ealt$ care costs" !6pectant
management results in prolonge antenatal $ospitalisation #$ile planne
earl( eliver( ma( necessitate intensive care of t$e neonate for problems
associate #it$ prematurit("
&et'ods(!esign- Be aim to evaluate t$e eLectiveness of earl( planne
birt$ compare #it$ e6pectant management for #omen #it$ PPROM
bet#een ,0 #ee<s an ,AA #ee<s gestation, in a ranomise controlle
trial" . seconar( aim is a cost anal(sis to establis$ t$e economic impact
of t$e t#o treatment options an establis$ t$e treatment preferences of
#omen #it$ PPROM close to term" T$e earl( planne birt$ group #ill be
elivere #it$in )0 $ours accoring to local management protocols" In t$e
e6pectant
management group birt$ #ill occur after spontaneous labour, at term or
#$en t$e attening clinician feels t$at birt$ is inicate accoring to usual
care" .ppro6imatel( +2+) #omen #it$ PPROM at ,03,AA #ee<s gestation
#ill be recruite for t$e trial" T$e primar( outcome of t$e stu( is neonatal
sepsis" Seconar( infant outcomes inclue respirator( istress, perinatal
mortalit(, neonatal intensive care unit amission, assiste ventilation an
earl( infant evelopment" Seconar( maternal outcomes inclue
c$orioamnionitis, postpartum infection treate #it$ antibiotics,
antepartum $aemorr$age, inuction of labour, moe of eliver(, maternal
satisfaction #it$ care, uration of $ospitalisation, an maternal #ellbeing
at four mont$s postpartum"
!iscussion- T$is trial #ill provie evience on t$e optimal care for #omen
#it$ PPROM close to term (,03,4 #ee<s gestation)" 'onsieration of bot$
t$e clinical an economic seNuelae of t$e management of PPROM #ill
enable informe ecision ma<ing an guieline evelopment"
Background- Preterm prelabour rupture of membranes (PPROM)
complicates up to )I of all pregnancies an is t$e cause of 0*I of all
preterm birt$s" T$e optimal management of #omen #it$ PPROM prior to
,4 #ee<s, is not <no#n" /urt$ermore, iversit( in current clinical practice
suggests uncertaint( about t$e appropriate clinical management" T$ere
are t#o options for managing PPROM, e6pectant management (a #ait an
see approac$) or earl( planne birt$" Infection is t$e main ris< for #omen
in #$ic$ management is e6pectant" T$is ris< nee to be balance against
t$e ris< of iatrogenic prematurit( if earl( eliver( is planne" T$e iLerent
treatment options ma( also $ave iLerent $ealt$ care costs" !6pectant
management results in prolonge antenatal $ospitalisation #$ile planne
earl( eliver( ma( necessitate intensive care of t$e neonate for problems
associate #it$ prematurit("
&et'ods(!esign- Be aim to evaluate t$e eLectiveness of earl( planne
birt$ compare #it$ e6pectant management for #omen #it$ PPROM
bet#een ,0 #ee<s an ,AA #ee<s gestation, in a ranomise controlle
trial" . seconar( aim is a cost anal(sis to establis$ t$e economic impact
of t$e t#o treatment options an establis$ t$e treatment preferences of
#omen #it$ PPROM close to term" T$e earl( planne birt$ group #ill be
elivere #it$in )0 $ours accoring to local management protocols" In t$e
e6pectant
management group birt$ #ill occur after spontaneous labour, at term or
#$en t$e attening clinician feels t$at birt$ is inicate accoring to usual
care" .ppro6imatel( +2+) #omen #it$ PPROM at ,03,AA #ee<s gestation
#ill be recruite for t$e trial" T$e primar( outcome of t$e stu( is neonatal
sepsis" Seconar( infant outcomes inclue respirator( istress, perinatal
mortalit(, neonatal intensive care unit amission, assiste ventilation an
earl( infant evelopment" Seconar( maternal outcomes inclue
c$orioamnionitis, postpartum infection treate #it$ antibiotics,
antepartum $aemorr$age, inuction of labour, moe of eliver(, maternal
satisfaction #it$ care, uration of $ospitalisation, an maternal #ellbeing
at four mont$s postpartum"
!iscussion- T$is trial #ill provie evience on t$e optimal care for #omen
#it$ PPROM close to term (,03,4 #ee<s gestation)" 'onsieration of bot$
t$e clinical an economic seNuelae of t$e management of PPROM #ill
enable informe ecision ma<ing an guieline evelopment"
MR 8, P M, '. ', V& /, Varat$ara:u"
Planne earl( birt$ versus e6pectant
management (#aiting) for prelabour
rupture of membranes at term (,4
#ee<s or more)" )**4
Sim$an 59, 'anavan TP" Preterm
premature rupture of membranes-
iagnosis, evaluation an management
strategies" International &ournal of
Obstetrics an =(naecolog(" )**H@++)"
Bac<groun - Prelabour rupture of
membranes at term is manage
e6pectantl( or b( elective birt$, but it is
not clear if #aiting for birt$ to occur
spontaneousl( is better t$an
intervening"
Ob:ectives -To assess t$e eLects of
planne earl( birt$ versus e6pectant
management for #omen #it$ term
prelabour rupture of membranes on
fetal, infant an maternal #ellbeing"
Searc$ strateg( - Be searc$e t$e
'oc$rane Pregnanc( an '$ilbirt$
=roup Trials Register (9ovember )**0),
t$e 'oc$rane 'entral Register of
'ontrolle Trials (T$e 'oc$rane >ibrar(,
Issue 0, )**0), M!8>I9! (+7AA to
9ovember )**0) an !MB.S! (+740 to
9ovember )**0)" Selection criteria
Ranomise or Nuasi1ranomise trials
of planne earl( birt$ compare #it$
e6pectant management in #omen #it$
prelabour rupture of membranes at ,4
#ee<sK gestation or more" 8ata
collection an anal(sis T#o revie#
aut$ors inepenentl( applie eligibilit(
criteria, assesse trial Nualit( an
e6tracte ata" . ranom1eLects moel
#as use"
Main results - T#elve trials (total of A2+0
#omen) #ere inclue" Planne
management #as generall( inuction
#it$ o6(tocin or prostaglanin, #it$ one
trial using omoeopat$ic caulop$(llum"
Overall, no iLerences #ere etecte for
moe of birt$ bet#een planne an
e6pectant groups- relative ris< (RR) of
caesarean section *"70, 7HIconCence
interval ('I) *"2) to +"*2 (+) trials, A2+0
#omen)@ RR of operative vaginal birt$
*"72, 7HI *"20 to +"+A (4 trials, HH++
#omen)" SigniCcantl( fe#er #omen in
t$e planne compare #it$ e6pectant
management groups $a
c$orioamnionitis (RR *"40, 7HI 'I *"HA
to *"74@ 7 trials, AA++ #omen) or
enometritis (RR *",*, 7HI 'I *"+) to
*"40@ 0 trials, 00H #omen)" 9o iLerence
#as seen for neonatal infection (RR
*"2,, 7HI'I *"A+ to +"+)@ 7 trials, A0*A
infants)" 5o#ever, fe#er infants uner
planne management #ent to neonatal
intensive or special care compare #it$
e6pectant management (RR *"4), 7HI
'I *"H4 to *"7), number neee to treat
)*@ H trials, HA47 infants)" In a single
trial, signiCcantl( more #omen #it$
planne management vie#e t$eir care
more positivel( t$an t$ose e6pectantl(
manage (RR of Onot$ing li<eP *"0H,
7HI 'I *",4 to *"H0@ H*,+ #omen)
Preterm premature rupture of t$e
membranes (PPROM) is responsible for
one1t$ir of all preterm birt$s an
aLects +)*,*** pregnancies in t$e
;nite States eac$ (ear" !Lective
treatment relies on accurate iagnosis
an is gestational age epenent" T$e
iagnosis of PPROM is mae b( a
combination of clinical suspicion,
patient $istor( an some simple tests"
PPROM is associate #it$ signiCcant
maternal an neonatal morbiit( an
mortalit( from infection, umbilical cor
compression, placental abruption an
preterm birt$" Subclinical intrauterine
infection $as been implicate as a
ma:or aetiological factor in t$e
pat$ogenesis an subseNuent maternal
an neonatal morbiit( associate #it$
PPROM" T$e freNuenc( of positive
cultures obtaine b( transabominal
amniocentesis at t$e time of
presentation #it$ PPROM in t$e
absence of labour is )H30*I" T$e
ma:orit( of amniotic %ui infection in
t$e setting of PPROM oes not prouce
t$e signs an s(mptoms traitionall(
use as iagnostic criteria for clinical
c$orioamnionitis" .n( evience of
infection b( amniocentesis s$oul be
consiere carefull( as an inication for
eliver(" 8ocumentation of amniotic
%ui infection in #omen #$o present
#it$ PPROM enables us to triage our
t$erapeutic ecision ma<ing rationall("
In PPROM, t$e optimal interval for
eliver( occurs #$en t$e ris<s of
immaturit( are out#eig$e b( t$e ris<s
of pregnanc( prolongation (infection,
abruption an cor accient)" >ung
maturit( assessment ma( be a useful
guie #$en planning eliver( in t$e ,)1
to ,01#ee< interval" . gestational age
approac$ to t$erap( is important an
s$oul be a:uste for eac$ $ospitalKs
neonatal intensive care unit" .ntenatal
antibiotics an corticosteroi t$erapies
$ave clear beneCts an s$oul be
oLere to all #omen #it$out
contrainications" 8uring conservative
management, #omen s$oul be
monitore closel( for placental
abruption, infection, labour an a non1
reassuring fetal status" Bomen #it$
PPROM after ,) #ee<s of gestation
s$oul be consiere for eliver(, an
after ,0 #ee<s t$e beneCts of eliver(
clearl( out#eig$ t$e ris<s"
Bac<groun - Prelabour rupture of
membranes at term is manage
e6pectantl( or b( elective birt$, but it is
not clear if #aiting for birt$ to occur
spontaneousl( is better t$an
intervening"
Ob:ectives -To assess t$e eLects of
planne earl( birt$ versus e6pectant
management for #omen #it$ term
prelabour rupture of membranes on
fetal, infant an maternal #ellbeing"
Searc$ strateg( - Be searc$e t$e
'oc$rane Pregnanc( an '$ilbirt$
=roup Trials Register (9ovember )**0),
t$e 'oc$rane 'entral Register of
'ontrolle Trials (T$e 'oc$rane >ibrar(,
Issue 0, )**0), M!8>I9! (+7AA to
9ovember )**0) an !MB.S! (+740 to
9ovember )**0)" Selection criteria
Ranomise or Nuasi1ranomise trials
of planne earl( birt$ compare #it$
e6pectant management in #omen #it$
prelabour rupture of membranes at ,4
#ee<sK gestation or more" 8ata
collection an anal(sis T#o revie#
aut$ors inepenentl( applie eligibilit(
criteria, assesse trial Nualit( an
e6tracte ata" . ranom1eLects moel
#as use"
Main results - T#elve trials (total of A2+0
#omen) #ere inclue" Planne
management #as generall( inuction
#it$ o6(tocin or prostaglanin, #it$ one
trial using omoeopat$ic caulop$(llum"
Overall, no iLerences #ere etecte for
moe of birt$ bet#een planne an
e6pectant groups- relative ris< (RR) of
caesarean section *"70, 7HIconCence
interval ('I) *"2) to +"*2 (+) trials, A2+0
#omen)@ RR of operative vaginal birt$
*"72, 7HI *"20 to +"+A (4 trials, HH++
#omen)" SigniCcantl( fe#er #omen in
t$e planne compare #it$ e6pectant
management groups $a
c$orioamnionitis (RR *"40, 7HI 'I *"HA
to *"74@ 7 trials, AA++ #omen) or
enometritis (RR *",*, 7HI 'I *"+) to
*"40@ 0 trials, 00H #omen)" 9o iLerence
#as seen for neonatal infection (RR
*"2,, 7HI'I *"A+ to +"+)@ 7 trials, A0*A
infants)" 5o#ever, fe#er infants uner
planne management #ent to neonatal
intensive or special care compare #it$
e6pectant management (RR *"4), 7HI
'I *"H4 to *"7), number neee to treat
)*@ H trials, HA47 infants)" In a single
trial, signiCcantl( more #omen #it$
planne management vie#e t$eir care
more positivel( t$an t$ose e6pectantl(
manage (RR of Onot$ing li<eP *"0H,
7HI 'I *",4 to *"H0@ H*,+ #omen)
Preterm premature rupture of t$e
membranes (PPROM) is responsible for
one1t$ir of all preterm birt$s an
aLects +)*,*** pregnancies in t$e
;nite States eac$ (ear" !Lective
treatment relies on accurate iagnosis
an is gestational age epenent" T$e
iagnosis of PPROM is mae b( a
combination of clinical suspicion,
patient $istor( an some simple tests"
PPROM is associate #it$ signiCcant
maternal an neonatal morbiit( an
mortalit( from infection, umbilical cor
compression, placental abruption an
preterm birt$" Subclinical intrauterine
infection $as been implicate as a
ma:or aetiological factor in t$e
pat$ogenesis an subseNuent maternal
an neonatal morbiit( associate #it$
PPROM" T$e freNuenc( of positive
cultures obtaine b( transabominal
amniocentesis at t$e time of
presentation #it$ PPROM in t$e
absence of labour is )H30*I" T$e
ma:orit( of amniotic %ui infection in
t$e setting of PPROM oes not prouce
t$e signs an s(mptoms traitionall(
use as iagnostic criteria for clinical
c$orioamnionitis" .n( evience of
infection b( amniocentesis s$oul be
consiere carefull( as an inication for
eliver(" 8ocumentation of amniotic
%ui infection in #omen #$o present
#it$ PPROM enables us to triage our
t$erapeutic ecision ma<ing rationall("
In PPROM, t$e optimal interval for
eliver( occurs #$en t$e ris<s of
immaturit( are out#eig$e b( t$e ris<s
of pregnanc( prolongation (infection,
abruption an cor accient)" >ung
maturit( assessment ma( be a useful
guie #$en planning eliver( in t$e ,)1
to ,01#ee< interval" . gestational age
approac$ to t$erap( is important an
s$oul be a:uste for eac$ $ospitalKs
neonatal intensive care unit" .ntenatal
antibiotics an corticosteroi t$erapies
$ave clear beneCts an s$oul be
oLere to all #omen #it$out
contrainications" 8uring conservative
management, #omen s$oul be
monitore closel( for placental
abruption, infection, labour an a non1
reassuring fetal status" Bomen #it$
PPROM after ,) #ee<s of gestation
s$oul be consiere for eliver(, an
after ,0 #ee<s t$e beneCts of eliver(
clearl( out#eig$ t$e ris<s"
Singla ., ?aav P, Vai 9B, Sune:a .,
Mo$amma, /arii" Transabominal
amnioinfusion in preterm premature
rupture of membranes" International
&ournal of =(necolog( an Obstetrics"
)*+*@+*2"
Ob:ective- To evaluate t$e eLect of
transabominal amnioinfusion on
prolongation of pregnanc(, an maternal
an neonatal outcomes in preterm
premature rupture of membranes
(pPROM)"
Met$os- Be conucte a prospective
ranomiGe controlle stu( of #omen
#it$ pPROM uring singleton live
pregnanc(Qbet#een )A an ,,RA #ee<s
Q#$ose amniotic %ui ine6 (./I) #as less
t$an t$e Ht$ percentile" T$e stu( group
uner#ent transabominal amnioinfusion
at amission an t$en #ee<l( if t$eir ./I
fell belo# t$e Ht$ percentile again" T$e
control group receive e6pectant
management"
Results- T$e iLerence in t$e mean
interval from pPROM to eliver( bet#een
t$e groups #as not statisticall( signiCcant"
9eonatal an maternal outcomes #ere
signiCcantl( improve in t$e stu( group
compare #it$ t$e control group (fetal
istress S+*I vs ,4IT@ earl( neonatal
sepsis S+4I vs A,IT@ neonatal mortalit(
S+4I vs A,IT@ spontaneous eliver( S2,I
vs H,IT@ an postpartum sepsis S4I vs
,,IT)" 'onclusion- Transabominal
amnioinfusion reuce fetal istress, earl(
neonatal sepsis, an neonatal mortalit(" In
t$e stu( group, more participants
elivere spontaneousl( an t$ere #ere
fe#er cases of postpartum sepsis,
alt$oug$ t$e pPROM3eliver( interval #as
not increase"
Ob:ective- To evaluate t$e eLect of
transabominal amnioinfusion on
prolongation of pregnanc(, an maternal
an neonatal outcomes in preterm
premature rupture of membranes
(pPROM)"
Met$os- Be conucte a prospective
ranomiGe controlle stu( of #omen
#it$ pPROM uring singleton live
pregnanc(Qbet#een )A an ,,RA #ee<s
Q#$ose amniotic %ui ine6 (./I) #as less
t$an t$e Ht$ percentile" T$e stu( group
uner#ent transabominal amnioinfusion
at amission an t$en #ee<l( if t$eir ./I
fell belo# t$e Ht$ percentile again" T$e
control group receive e6pectant
management"
Results- T$e iLerence in t$e mean
interval from pPROM to eliver( bet#een
t$e groups #as not statisticall( signiCcant"
9eonatal an maternal outcomes #ere
signiCcantl( improve in t$e stu( group
compare #it$ t$e control group (fetal
istress S+*I vs ,4IT@ earl( neonatal
sepsis S+4I vs A,IT@ neonatal mortalit(
S+4I vs A,IT@ spontaneous eliver( S2,I
vs H,IT@ an postpartum sepsis S4I vs
,,IT)" 'onclusion- Transabominal
amnioinfusion reuce fetal istress, earl(
neonatal sepsis, an neonatal mortalit(" In
t$e stu( group, more participants
elivere spontaneousl( an t$ere #ere
fe#er cases of postpartum sepsis,
alt$oug$ t$e pPROM3eliver( interval #as
not increase"
Stuart !>, !vans =S, >in ?S, Po#ers 5&" Reuce
'ollagen an .scorbic .ci 'oncentrations an
Increase Proteol(tic Susceptibilit( #it$ Prelabor
/etal Membrane Rupture in Bomen" BIO>O=? O/
R!PRO8;'TIO9" )**0@4)"
Prelabor rupture of t$e fetal membranes aLects
appro6imatel( +*I of #omen at term, resulting in
an increase ris< of maternal an neonatal
infection" !vience suggests t$at membrane
rupture is relate to bioc$emical processes
involving t$e e6tracellular matri6 of t$e
membranes" Be teste t$e $(pot$esis t$at
prelabor rupture membranes are c$aracteriGe
b( reuce collagen concentrations, altere
collagen cross1lin< proCles, an increase
concentrations of biomar<ers of o6iative amage"
Be also set out to etermine #$et$er t$ese
eLects are moulate b( ascorbic aci status" In a
case1control stu(, #e e6plore t$e role t$at
ascorbic aci, o6iative stress, collagen, an
collagen cross1lin<s pla( in etermining membrane
integrit( an evelope a functional assa( to
assess membrane proteol(tic susceptibilit("
Prelabor rupture membrane $a a reuce
ascorbic aci concentration in comparison #it$
controls #$ile protein carbon(l an
maloniale$(e concentrations #ere increase"
'ollagen concentrations #ere also reuce in
prelabor rupture membrane, an #$ile t$e
concentration of collagen cross1lin<s #as not
signiCcantl( iLerent bet#een prelabor an timel(
rupture membrane, t$ere #as a regional variation
in cross1lin< ratio #it$in t$e amniotic sac"
Proteol(tic resistance in vitro #as reuce in
prelabor rupture membrane an also e6$ibite
regional variation #it$in
t$e amniotic sac" Our Cnings are strongl(
supportive of a role for t$e en$ance egraation
of membrane collagen in t$e etermination of
prelabor rupture of fetal membranes" T$e
formation of t$e rupture initiation site is a function
of a regional variation in collagen cross1lin< ratio"
Tissue ascorbic aci status ma( be an important
meiator of t$ese processes"
conceptus, pregnanc(
Prelabor rupture of t$e fetal membranes aLects
appro6imatel( +*I of #omen at term, resulting in
an increase ris< of maternal an neonatal
infection" !vience suggests t$at membrane
rupture is relate to bioc$emical processes
involving t$e e6tracellular matri6 of t$e
membranes" Be teste t$e $(pot$esis t$at
prelabor rupture membranes are c$aracteriGe
b( reuce collagen concentrations, altere
collagen cross1lin< proCles, an increase
concentrations of biomar<ers of o6iative amage"
Be also set out to etermine #$et$er t$ese
eLects are moulate b( ascorbic aci status" In a
case1control stu(, #e e6plore t$e role t$at
ascorbic aci, o6iative stress, collagen, an
collagen cross1lin<s pla( in etermining membrane
integrit( an evelope a functional assa( to
assess membrane proteol(tic susceptibilit("
Prelabor rupture membrane $a a reuce
ascorbic aci concentration in comparison #it$
controls #$ile protein carbon(l an
maloniale$(e concentrations #ere increase"
'ollagen concentrations #ere also reuce in
prelabor rupture membrane, an #$ile t$e
concentration of collagen cross1lin<s #as not
signiCcantl( iLerent bet#een prelabor an timel(
rupture membrane, t$ere #as a regional variation
in cross1lin< ratio #it$in t$e amniotic sac"
Proteol(tic resistance in vitro #as reuce in
prelabor rupture membrane an also e6$ibite
regional variation #it$in
t$e amniotic sac" Our Cnings are strongl(
supportive of a role for t$e en$ance egraation
of membrane collagen in t$e etermination of
prelabor rupture of fetal membranes" T$e
formation of t$e rupture initiation site is a function
of a regional variation in collagen cross1lin< ratio"
Tissue ascorbic aci status ma( be an important
meiator of t$ese processes"
conceptus, pregnanc(
Bang 5, Parr( S, Macones =, Sammel M8,
Kuivaniemi 5, Tromp =, et al" . functional S9P in t$e
promoter of t$e S!RPI95+ gene increases ris< of
preterm premature rupture of membranes in .frican
.mericans )**A
Prematurit( is more prevalent in .frican .mericans
t$an in !uropean .mericans" Be investigate t$e
contribution of a functional S9P in t$e promoter of
t$e S!RPI95+ gene, enric$e among t$ose of
.frican ancestr(, to preterm premature rupture of
membranes (PPROM), t$e leaing ientiCable cause
of preterm birt$" S!RPI95+ encoes $eat1s$oc<
protein 04, a c$aperone essential for collagen
s(nt$esis" T$e S!RPI95+ AHA minor T allele $a a
greater freNuenc( in .frican populations an .frican
.mericans t$an in !uropean .mericans (+)"0I vs"
0"+I)" T$e AHA T allele ispla(e signiCcantl(
reuce promoter activit( compare to t$e ma:or
AHA ' allele in amnion Cbroblasts, #$ic$ la( o#n
t$e Cbrillar collagen t$at gives tensile strengt$ to
t$e amnion" .n initial case1control stu(
emonstrate t$at t$e AHA T allele is signiCcantl(
more freNuent in .frican1.merican neonates (P U
*"***7) born from pregnancies complicate b(
PPROM compare #it$ controls (os ratio of ,")),
7HI conCence interval +"H*, 4")))" T$ere #as no
signiCcant iLerence in ancestr( among cases an
controls using a i$(bri moel base on )7
ancestr(1informative mar<ers" .:usting t$e results
of t$e case1control stu( for ami6ture still (iele
a statisticall( signiCcant association bet#een t$e
AHA T allele an PPROM (P U *"**))" . follo#1up
case1control stu( gave similar results" T$e
combine case1control Cnings s$o#e a $ig$l(
signiCcant (P U *"*****0H) association bet#een t$e
AHA T allele an PPROM" T$e S!RPI95+ AHA T
allele is t$e Crst e6ample of an ancestr(1informative
mar<er associate #it$ preterm birt$ in .frican
.mericans"
Prematurit( is more prevalent in .frican .mericans
t$an in !uropean .mericans" Be investigate t$e
contribution of a functional S9P in t$e promoter of
t$e S!RPI95+ gene, enric$e among t$ose of
.frican ancestr(, to preterm premature rupture of
membranes (PPROM), t$e leaing ientiCable cause
of preterm birt$" S!RPI95+ encoes $eat1s$oc<
protein 04, a c$aperone essential for collagen
s(nt$esis" T$e S!RPI95+ AHA minor T allele $a a
greater freNuenc( in .frican populations an .frican
.mericans t$an in !uropean .mericans (+)"0I vs"
0"+I)" T$e AHA T allele ispla(e signiCcantl(
reuce promoter activit( compare to t$e ma:or
AHA ' allele in amnion Cbroblasts, #$ic$ la( o#n
t$e Cbrillar collagen t$at gives tensile strengt$ to
t$e amnion" .n initial case1control stu(
emonstrate t$at t$e AHA T allele is signiCcantl(
more freNuent in .frican1.merican neonates (P U
*"***7) born from pregnancies complicate b(
PPROM compare #it$ controls (os ratio of ,")),
7HI conCence interval +"H*, 4")))" T$ere #as no
signiCcant iLerence in ancestr( among cases an
controls using a i$(bri moel base on )7
ancestr(1informative mar<ers" .:usting t$e results
of t$e case1control stu( for ami6ture still (iele
a statisticall( signiCcant association bet#een t$e
AHA T allele an PPROM (P U *"**))" . follo#1up
case1control stu( gave similar results" T$e
combine case1control Cnings s$o#e a $ig$l(
signiCcant (P U *"*****0H) association bet#een t$e
AHA T allele an PPROM" T$e S!RPI95+ AHA T
allele is t$e Crst e6ample of an ancestr(1informative
mar<er associate #it$ preterm birt$ in .frican
.mericans"

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